Gaucher's Disease

Gaucher's Disease

A 65-year-old man with no significant medical history presented with mild abdominal pain—primarily in the left lower quadrant—and bleeding gums. He had a petechial rash over the entire body and hepatosplenomegaly 10 cm below the costal margin. Laboratory work-up disclosed a hemoglobin level of 10 g/dL, a white blood cell count of 7,700/mL, and a platelet count of 50,000/mL; serum chemistry values were normal. Bone marrow aspiration revealed heavy infiltration of large cells with blue cytoplasm and multiple eccentric nuclei. There were numerous microfibrils in the cytoplasm.

Drs Hesham Taha and Gamil Kostandy of Brooklyn, NY, diagnosed this condition as Gaucher's disease, type 1. They comment that Gaucher's disease is the most prevalent hereditary metabolic storage disorder, and it is inherited as an autosomal recessive trait. All affected patients have a genetic defect in the enzyme glucocerebrosidase, which results in accumulation of the glucocerebroside lipids within the reticuloendothelial cells (known as Gaucher's cells). Pictured here are typical Gaucher's cells, characterized by multiple eccentrically placed nuclei with numerous fibrillae in the cytoplasm.1,2 These tissue macrophages may be present in the spleen, bone marrow, liver, and lung.

Gaucher's disease is classified into three major types, based on clinical signs and symptoms. Type 1 is the adult or chronic non-neuronopathic form; type 2 is the infantile acute neuronopathic form; and type 3 is the juvenile subacute neuronopathic disorder. The disease's clinical signs and symptoms may vary greatly depending on the type; even the same type can have different manifestations in different patients.

Patients with type 1 disease may present with a combination of anemia, low platelet count, massively enlarged liver and spleen, and extensive skeletal disease; or the patient may be completely asymptomatic and the disease discovered accidentally during evaluation for another condition.3,4 The choice of treatment modality depends on the clinical picture: hydration, analgesics and narcotics for pain, orthopedic surgery for fracture repair, and blood transfusion for anemia are among the options. Bone marrow transplantation is effective, but the risk of morbidity and mortality is high. Patients with Gaucher's disease type 1 also may benefit from enzyme replacement therapy with purified placental glucocerebrosidase and gene therapy. This patient's condition showed clinical improvement following enzyme replacement therapy.5